Chronic obstructive pulmonary disease (COPD), including asthma, chronic bronchitis and emphysema, affects an estimated 330 million people worldwide. COPD has been and is projected to continue to be the third leading cause of death in the next two decades.
Management of COPDs necessarily involves periodic and precise administration and dosing of therapeutic agents delivered into respiratory airways. These agents are generally administered by aerosol formulations through the mouth or nose. One device for dispensing aerosol drug formulations is called a pressurized metered-dose inhaler (pMDI). A drug formulation is suspended in liquefied gas known as a propellant. This suspension is stored at a pressure which maintains the propellant in a liquid state within a sealed container capable of withstanding this pressure. The container is connected to a dose metering valve that, when activated, dispenses a predetermined amount of aerosolized suspension into the respiratory airway. Active drug ingredients commonly used in pMDIs include corticosteroids and bronchodilators, for example β2 adrenergic receptor antagonists and muscarinic receptor antagonists. The pMDIs can contain one or more active ingredients.
The liquefied pMDI propellant, being gaseous at atmospheric pressure, serves two major purposes: it is the vehicle that suspends and carries the therapeutic components and it aerosolizes and propels the drugs into respiratory airways upon gasification following actuation of the pMDI metering valve. The typical vapor pressure inside a pMDI ranges from 400 to 700 kPa (4 to 7 atm), depending on the propellant mixture, ambient temperature and the specific formulation. Ozone-layer-damaging chlorofluorocarbons (CFCs) were first used as pMDI propellants but have been gradually phased out over the years in favor of hydrofluoroalkanes (HFAs). However, since HFAs are greenhouse gases, the search for the next generation of pMDI propellants is ongoing.
There are many factors that can affect the proper dosage and delivery of the drug formulations contained within a pMDI, from malfunctioning metering valves to adherence of aerosol drugs to the inner surfaces of the container to manufacturing defects. Also the stability of the therapeutic suspensions in pMDI propellants has important consequences for drug efficacy and safety.
Challenges to proper dosing and dispensing of medications from pMDIs must be addressed in an efficient manner to provide the proper treatment to COPD patients. Further, it is required that the prescribed dose of aerosol medication delivered to the patient consistently meets the specifications required by regulating agencies such as the U.S. Food and Drug administration as well as the prescribing medical professional. Quality assurance methods for the measurement of the proper delivered dose have been developed, see for example U.S. Pat. No. 5,261,538, “Aerosol testing method,” issued Nov. 16, 1993. In order to discourage adherence of the drug formulation to the walls of pMDI container special coatings have been developed specific to individual drug formulations as discussed in U.S. Pat. No. 6,253,762, “Metered dose inhaler for fluticasone propionate,” Issued Jul. 3, 2001. With the goal to provide quality assurance in pMDIs and to aid in the search for propellants to be used in these devices, the present invention provides a method to test the stability of the therapeutic suspensions within a pMDI.